Multidrug Therapy Regimens Research Articles

Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy

SummaryBackgroundTreatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT.MethodsAn analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT.ResultsIn skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%.ConclusionPersistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF.

Comparative host transcriptomics as a tool to identify candidate biomarkers for immune reactions in leprosy using meta-analysis.

Background Leprosy is no longer considered an imprecation, as an effective multidrug therapy regimen is available worldwide for its cure. However, its diverse clinical manifestations sometimes involve acute inflammatory reactions. These complications result in irreversible nerve damage, neuritis and anatomical deformities that emerge before, during the treatment or after the completion of treatment. Reversal reaction (Type-I) and erythema nodosum leprosum (Type-II) are the leprosy reactions generally seen in patients with lepromatous and borderline forms of leprosy. At present, there is no accurate diagnostic test available to detect these leprosy reactions. Objectives To identify potential biomarkers indicative of Type-I and Type-II leprosy reactions that could help in their early diagnosis. Methods and Results Host-transcriptomics investigations have been utilised in this study to decipher a correlation between host-gene expression-based biomarkers and exacerbation of leprosy reactions. We present a comparative analysis of publicly available host transcriptomics datasets (from Gene Expression Omnibus) related to leprosy reactions. Individual datasets were analysed and integration of results was carried out using meta-analysis. Common differentially expressed genes (DEGs) were identified using the frequentist and Bayesian ratio association test methods. We have identified several genes - ADAMTS5, ADAMTS9, IFITM2, IFITM3, KIRREL, ANK3, CD1E, CTSF, DOCK9 and KRT73 to name a few - which can serve as potential biomarkers for Type-II reaction. Similarly, ACP5, APOC1, CCL17, S100B, SLC11A1 among others may likely serve as biomarkers for Type-I reaction. Limitations The number of datasets related to leprosy reactions found after the systematic search is less (n = 4) and may limit the accuracy of identified biomarker genes. This could be resolved by including more studies in the data analysis. Conclusion We provide a comprehensive list of gene candidates which could be prioritised further in research focusing on immune reactions in leprosy, as they are likely important in understanding its complexities and could be useful in its early diagnosis.

High frequency of ofloxacin resistance patterns of Mycobacterium leprae from India: An indication to revisit second line anti-leprosy treatment regimen

Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive=67, with persistent skin lesions=35, with recurrence=34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.

Recurrent choriocarcinoma complicated with leprosy during chemotherapy: A case report and literature review.

The global prevalence of leprosy has decreased substantially, and cases of leprosy infection are extremely rare in China. In this report, we present a case of recurrent choriocarcinoma complicated by leprosy infection during chemotherapy. A 24-year-old Chinese woman (gravida 3, para 2) presented to a local hospital with vaginal bleeding. Her medical history included a previous diagnosis of hydatidiform mole. The patient was diagnosed with choriocarcinoma and received chemotherapy in 6 cycles. Shortly after the initial treatment was completed, the disease recurred twice with resistance to multiple chemotherapeutic agents. In her second recurrence of choriocarcinoma, she was diagnosed with leprosy with many cutaneous nodules throughout her entire body. The patient was administered chemical treatment for leprosy with the multidrug therapy regimen after being diagnosed. To prevent exacerbating the infection, no immunotherapy was utilized to treat cancer, and the infection was well-controlled at the conclusion of anticancer therapy. Because of immunological reduction, cancer patients are susceptible to a variety of infections. For patients with cancer, prevention and early detection of rare infectious diseases should receive special attention. Immunotherapy must be used with caution when treating patients with cancer and infections.

Comparison between lymecycline with multidrug therapy and standard multidrug regimen (WHO-MDT) in the treatment of multibacillary leprosy patients: a retrospective cohort study.

Hansen's disease or leprosy is a chronic, infectious disease that has locally and globally afflicted all populations. Despite standard treatment with multidrug therapy (WHO-MDT), the incidence of drug resistance has been an increasingly prevalent global problem in leprosy management. This study compared the effectiveness between lymecycline with WHO-MDT and standard WHO-MDT in leprosy treatment. The research is a retrospective cohort study at a tertiary hospital from January 2011 to July 2021. Pre- and post-treatment bacillary index, presence of new lesions, nerve function impairment, and leprosy reactions were obtained through chart review. The results showed a significant difference in bacteriological index (BI) in both groups at the end of the treatment. However, a higher reduction in BI was noted for the lymecycline group. For the group that took WHO-MDT alone, BI decreased by 0.7 (P < 0.001) whereas patients who took lymecycline and WHO-MDT had a BI difference of 3 (P < 0.001) upon completion of treatment. A significant decrease in the recurrence of lesions (P = 0.006) and nerve function impairment (P = 0.038) was also noted in the lymecycline group whereas there was no significant difference in leprosy reactions between the two groups. Lymecycline 600 mg daily for 3 months can be used as an adjunct in cases of leprosy resistance and treatment failure among multibacillary patients. Lymecycline significantly reduced bacillary index, recurrence of skin lesions, and nerve function impairment through its possible immunomodulatory, antiapoptotic, and neuroprotective effects.

Interaction between leprosy and HIV infection

Introduction: Leprosy and Human Immunodeficiency Virus (HIV) infections still count as major health issues worldwide. Starting with the HIV pandemic back in the eighties, leprosy was feared to re-emerge as the HIV cases arose. Co-infections between leprosy and HIV were worried to cause an increase in leprosy cases, with worse clinical manifestation, predominantly toward the lepromatous spectrum, decrease in therapy response, and prolonged therapy period. Unlike its interaction with tuberculosis, HIV infection was turned out to not increasing nor deteriorating the manifestation of leprosy infection. All clinical spectrum of leprosy was found in HIV infection patients without predomination of lepromatous type. Responses to leprosy Multi-Drug Therapy (MDT) regimen were also found similar between leprosy patients with or without HIV.&#x0D; Conclusion: It is recommended to treat co-infective patients both with leprosy MDT and antiretroviral therapy. Manifestation of leprosy as a part of immune reconstitution syndrome need more attention and investigation.

Low risk of relapse and deformity among leprosy patients who completed multi-drug therapy regimen from 2005 to 2010: A cohort study from four districts in South India.

IntroductionRelapse of leprosy among patients released from treatment (RFT) is an indicator of the success of anti-leprosy treatment. Due to inadequate follow-up, relapse in leprosy patients after RFT is not systematically documented in India. Relapsed leprosy patients pose a risk in the transmission of leprosy bacilli. We determined the incidence of relapse and deformity among the patients RFT from the leprosy control programme in four districts in South India.MethodsWe conducted two follow-up surveys in 2012 and 2014 among the leprosy patients RFT between 2005 and 2010. We assessed them for any symptoms or signs of relapse, persistence and deformity. We collected slit skin samples (SSS) for smear examination. We calculated overall incidence of relapse and deformity per 1000 person-years (PY) with 95% confidence intervals (CI) and cumulative risk of relapse.ResultsOverall, we identified 69 relapse events, 58 and 11, during the first and second follow-up surveys, respectively. The incidence of relapse was 5.42 per 1000 PY, which declined over the years after RFT. The cumulative risk of relapse was 2.24%. The rate of deformity among the relapsed patients was 30.9%. The overall incidence of deformity was 1.65 per 1000 person years. The duration of M. leprae detection in smears ranged between 2.38 and 7.67 years.ConclusionsLow relapse and deformity rates in leprosy RFT patients are indicative of treatment effectiveness. However, a higher proportion of detection of deformity among relapsed cases is a cause for concern. Periodic follow-up of RFT patients for up to 3 years to detect relapses early and ensure appropriate treatment will minimize the development of deformity among relapsed patients.

Interaction of constituents of MDT regimen for leprosy with Mycobacterium leprae HSP18: impact on its structure and function

Mycobacterium leprae, the causative organism of leprosy, harbors many antigenic proteins, and one such protein is the 18-kDa antigen. This protein belongs to the small heat shock protein family and is commonly known as HSP18. Its chaperone function plays an important role in the growth and survival of M. leprae inside infected hosts. HSP18/18-kDa antigen is often used as a diagnostic marker for determining the efficacy of multidrug therapy (MDT) in leprosy. However, whether MDT drugs (dapsone, clofazimine, and rifampicin) do interact with HSP18 and how these interactions affect its structure and chaperone function is still unclear. Here, we report evidence of HSP18-dapsone/clofazimine/rifampicin interaction and its impact on the structure and chaperone function of HSP18. These three drugs interact efficiently with HSP18 (having submicromolar binding affinity) with 1 : 1 stoichiometry. Binding of these MDT drugs to the 'α-crystallin domain' of HSP18 alters its secondary structure and tryptophan micro-environment. Furthermore, surface hydrophobicity, oligomeric size, and thermostability of the protein are reduced upon interaction with these three drugs. Eventually, all these structural alterations synergistically decrease the chaperone function of HSP18. Interestingly, the effect of rifampicin on the structure, stability, and chaperone function of this mycobacterial small heat shock protein is more pronounced than the other two MDT drugs. This reduction in the chaperone function of HSP18 may additionally abate M. leprae survivability during multidrug treatment. Altogether, this study provides a possible foundation for rational designing and development of suitable HSP18 inhibitors in the context of effective treatment of leprosy.

The Dermlep Study Part 2: Results of a Nation-Wide Survey of Dermatologists' Access to Quality Leprosy Services at their Clinics and Hospitals in India.

Introduction:Dermatologists in India are trained and qualified to treat leprosy and there is evidence to suggest that they are involved in the diagnosis and management of a significant number of leprosy patients in the country. The present study evaluated the access to quality leprosy services at their clinics and hospitals to understand the extent of their role in providing comprehensive care to people affected by leprosy and how it can be organized further.Methods:The DermLep Study was a pan-India questionnaire-based survey carried out to evaluate the role that dermatologists play in leprosy management in the country. It included as part-2 of the survey, 11 questions on the access of the dermatologist to various quality leprosy services available at the clinic or institution including skin smears, skin biopsy, multidrug therapy (MDT) blister packs, basic physiotherapy services, and reporting to the national program (NLEP).Results:The dermatologists who participated in the survey included 101 private practitioners and 100 working in Government or private medical institutions. The key findings of the survey were that 78% of the participating dermatologists still encounter leprosy patients frequently in their clinics; 81.0% of them had access to skin smears; and 93.4% to skin biopsy. The World Health Organization (WHO) MDT regimen was followed by 79.0% of the dermatologists in the study, majority of whom were those working in medical colleges (88%); however overall, 87.4% extended the regimen beyond the fixed duration, mostly on a case to case basis. Thalidomide was available for 61.1% of them to treat type 2 reactions. Basic physiotherapy services were available with 70.2% of dermatologists surveyed; 58.9% dermatologists had access to MCR footwear; and RCS facility access known to 45.5% of them. About 83.5% of the dermatologists working in institutions were reporting their leprosy cases to the NLEP, whereas from a high percentage (71.4%) of dermatologists in private practice, cases were not captured in routine under NLEP.Conclusion:Dermatologists in India have the clinical skill, expertise, and access to most of the basic services, including skin smear and skin biopsy facilities needed to provide comprehensive care to leprosy patients in post-elimination era of integration of leprosy services. While dermatologists are already managing leprosy patients both at medical institutes and private clinics across India, their “structured” involvement at all levels in the national program will facilitate improved reporting and cataloging of cases seen by them. It will also elevate standards of leprosy care; create an effective public-private partnership and disease expertise; and assist develop a comprehensive, patient-tailored approach in the leprosy program in India.

Glucocorticoids in Leprosy Reversal reaction

Abstract Leprosy is a disease that is caused by Mycobacterium leprae which results in lots of disabilities in the patients. Leprosy is treated by multi-drug therapy regimen; however, this therapy might cause leprosy reactions in the patients. There are several types of lepromatous reaction: type 1 reaction, type 2 reaction and neuritis. Type 1 reaction mainly occurs in BB, BL and BT forms of leprosy and is characterized by exacerbation of preexisting lesions. The therapy of this reaction according to the WHO guideline is corticosteroid therapy. This article will explain several key points related to the corticosteroid therapy in leprosy reversal reactions, including the side effects and alternative therapies available.

Mycobacterium leprae-Specific Antibodies in Multibacillary Leprosy Patients Decrease During and After Treatment With Either the Regular 12 Doses Multidrug Therapy (MDT) or the Uniform 6 Doses MDT.

Leprosy serology reflects the bacillary load of patients and multidrug therapy (MDT) reduces Mycobacterium leprae-specific antibody titers of multibacillary (MB) patients. The Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil (U-MDT/CT-BR) compared outcomes of regular 12 doses MDT/R-MDT and the uniform 6 doses MDT/U-MDT for MB leprosy, both of regimens including rifampicin, clofazimine, and dapsone. This study investigated the impact of R-MDT and U-MDT and the kinetic of antibody responses to M. leprae-specific antigens in MB patients from the U-MDT/CT-BR. We tested 3,400 serum samples from 263 MB patients (R-MDT:121; U-MDT:142) recruited at two Brazilian reference centers (Dona Libânia, Fortaleza, Ceará; Alfredo da Matta Foundation, Manaus, Amazonas). Enzyme-linked immunosorbent assays with three M. leprae antigens [NT-P-BSA: trisaccharide-phenyl of phenollic glycolipid-I antigen (PGL-I); LID-1: Leprosy Infectious Disease Research Institute Diagnostic 1 di-fusion recombinant protein; and ND-O-LID: fusion complex of disaccharide-octyl of PGL-I and LID-1] were performed using around 13 samples per patient. Samples were collected at baseline/M0, during MDT (R-MDT:M1–M12 months, U-MDT:M1–M6 months) and after MDT discontinuation (first, second year). Statistical significance was assessed by the Mann–Whitney U test for comparison between groups (p values < 0.05). Mixed effect multilevel regression analyses were used to investigate intraindividual serological changes overtime. In R-MDT and U-MDT groups, males predominated, median age was 41 and 40.5 years, most patients were borderline lepromatous and lepromatous leprosy (R-MDT:88%, U-MDT: 90%). The bacilloscopic index at diagnosis was similar (medians: 3.6 in the R-MDT and 3.8 in the U-MDT group). In R-MDT and U-MDT groups, a significant decline in anti-PGL-I positivity was observed from M0 to M5 (p = 0.035, p = 0.04, respectively), from M6 to M12 and at the first and second year posttreatment (p < 0.05). Anti-LID-1 antibodies declined from M0 to M6 (p = 0.024), M7 to M12 in the R-MDT; from M0 to M4 (p = 0.003), M5 to M12 in the U-MDT and posttreatment in both groups (p > 0.0001). Anti-ND-O-LID antibodies decreased during and after treatment in both groups, similarly to anti-PGL-I antibodies. Intraindividual serology results in R-MDT and U-MDT patients showed that the difference in serology decay to all three antigens was dependent upon time only. Our serology findings in MB leprosy show that regardless of the duration of the U-MDT and R-MDT, both of them reduce M. leprae-specific antibodies during and after treatment. In leprosy, antibody levels are considered a surrogate marker of the bacillary load; therefore, our serological results suggest that shorter U-MDT is also effective in reducing the patients’ bacillary burden similarly to R-MDT.Clinical Trial RegistrationClinicalTrials.gov, NCT00669643.

Interaction between leprosy and HIV infection

Introduction: Leprosy and Human Immunodeficiency Virus (HIV) infections still count as major health issues worldwide. Starting with the HIV pandemic back in the eighties, leprosy was feared to re-emerge as the HIV cases arose. Co-infections between leprosy and HIV were worried to cause an increase in leprosy cases, with worse clinical manifestation, predominantly toward the lepromatous spectrum, decrease in therapy response, and prolonged therapy period. Unlike its interaction with tuberculosis, HIV infection was turned out to not increasing nor deteriorating the manifestation of leprosy infection. All clinical spectrum of leprosy was found in HIV infection patients without predomination of lepromatous type. Responses to leprosy Multi-Drug Therapy (MDT) regimen were also found similar between leprosy patients with or without HIV.Conclusion: It is recommended to treat co-infective patients both with leprosy MDT and antiretroviral therapy. Manifestation of leprosy as a part of immune reconstitution syndrome need more attention and investigation.Keywords: HIV infection, leprosy, interaction

Clofazimine in Nontuberculous Mycobacterial Infections: A Growing Niche.

Infection secondary to rapidly growing mycobacteria (RGM) is associated with significant morbidity and mortality, especially in individuals with underlying structural lung disease or immune compromise. Such infections, particularly those caused by the Mycobacterium abscessus group, are challenging to treat due to high virulence, antibiotic resistance, and the lack of effective and tolerable therapies. Although novel antimycobacterials are under development, clofazimine—a drug historically administered as part of multidrug therapy regimens for Mycobacterium leprae—holds promise as a chemotherapeutic for the treatment of RGM. The history, pharmacologic properties of clofazimine, as well as in vitro and in vivo studies against RGM are described here and highlight a potential new niche for an old drug.

Leprosy reactions: The predictive value of Mycobacterium leprae-specific serology evaluated in a Brazilian cohort of leprosy patients (U-MDT/CT-BR).

BackgroundLeprosy reactions, reversal reactions/RR and erythema nodosum leprosum/ENL, can cause irreversible nerve damage, handicaps and deformities. The study of Mycobacterium leprae-specific serologic responses at diagnosis in the cohort of patients enrolled at the Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil/U-MDT/CT-BR is suitable to evaluate its prognostic value for the development of reactions.MethodologyIgM and IgG antibody responses to PGL-I, LID-1, ND-O-LID were evaluated by ELISA in 452 reaction-free leprosy patients at diagnosis, enrolled and monitored for the development of leprosy reactions during a total person-time of 780,930 person-days, i.e. 2139.5 person-years, with a maximum of 6.66 years follow-up time.Principal findingsAmong these patients, 36% (160/452) developed reactions during follow-up: 26% (119/452) RR and 10% (41/452) had ENL. At baseline higher anti-PGL-I, anti-LID-1 and anti-ND-O-LID seropositivity rates were seen in patients who developed ENL and RR compared to reaction-free patients (p<0.0001). Seroreactivity in reactional and reaction-free patients was stratified by bacilloscopic index/BI categories. Among BI negative patients, higher anti-PGL-I levels were seen in RR compared to reaction-free patients (p = 0.014). In patients with 0<BI<3, (36 RR, 36 reaction-free), higher antibody levels to PGL-I (p = 0.014) and to LID-1 (p = 0.035) were seen in RR while difference in anti-ND-O-LID positivity was borderline (p = 0.052). Patients with BI≥3 that developed ENL had higher levels of anti-LID-1 antibodies (p = 0.028) compared to reaction-free patients. Anti-PGL-I serology had a limited predictive value for RR according to receiver operating curve/ROC analyses (area-under-the-curve/AUC = 0.7). Anti LID-1 serology at baseline showed the best performance to predict ENL (AUC 0.85).ConclusionsOverall, detection of anti-PGL-I, anti-LID-1 and anti-ND-O-LID antibodies at diagnosis, showed low sensitivity and specificity for RR prediction, indicating low applicability of serological tests for RR prognosis. On the other hand, anti-LID-1 serology at diagnosis has shown prognostic value for ENL development in BI positive patients.Trial RegistrationClinicalTrials.gov NCT00669643

Leprosy among children under 15 years of age: literature review.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, representing a public health issue in some countries. Though more prevalent in adults, the detection of new cases in children under 15 years of age reveals an active circulation of bacillus, continued transmission and lack of disease control by the health system, as well as aiding in the monitoring of the endemic. Among patients under 15 years of age, the most affected age group is children between 10 and 14 years of age, although cases of patients of younger than 1 year of age have also been reported. Household contacts are the primary source of infection, given that caretakers, such as babysitters and others, must be considered in this scenario. Paucibacillary forms of the disease prevailed, especially borderline-tuberculoid leprosy, with a single lesion in exposed areas of the body representing the main clinical manifestation. Reactional states: Lepra reactions are rare, although some authors have reported high frequencies of this phenomenon, the most frequent of which is Type 1 Lepra Reaction. Peripheral nerve involvement has been described at alarming rates in some studies, which increases the chance of deformities, a serious problem, especially if one considers the age of these patients. The protective effect of BCG vaccination was found in some studies, but no consensus has been reached among different authors. Children must receive the same multidrug therapy regimen and the doses should, ideally, be calculated based on the child´s weight. Adverse reactions to this therapy are rare within this age group. This article aims to review epidemiological, clinical, and therapeutic aspects of leprosy in patients under 15 years of age.

Combination chemoprophylaxis and immunoprophylaxis in reducing the incidence of leprosy.

Leprosy is a complex infectious disease caused by Mycobacterium leprae that is a leading cause of nontraumatic peripheral neuropathy. Current control strategies, with a goal of early diagnosis and treatment in the form of multidrug therapy, have maintained new case reports at ~225,000 per year. Diagnostic capabilities are limited and even with revisions to multidrug therapy regimen, treatment can still require up to a year of daily drug intake. Although alternate chemotherapies or adjunct immune therapies that could provide shorter or simpler treatment regimen appear possible, only a limited number of trials have been conducted. More proactive strategies appear necessary in the drive to elimination. As a prevention strategy, most chemoprophylaxis campaigns to date have provided about a 2-year protective window. Vaccination, in the form of a single bacillus Calmette–Guérin (BCG) immunization, generally provides ~50% reduction in leprosy cases. Adapting control strategies to provide both chemoprophylaxis and immunoprophylaxis has distinct appeal, with chemoprophylaxis theoretically buttressed by vaccination to generate immediate protection that can be sustained in the long term. We also discuss simple assays measuring biomarkers as surrogates for disease development or replacements for invasive, but not particularly sensitive, direct measures of M. leprae infection. Such assays could facilitate the clinical trials required to develop these new chemoprophylaxis, immunoprophylaxis strategies, and transition into wider use.

History of chemotherapy of leprosy

Chemotherapy of leprosy over the past 70 years has passed through several phases, from sulfones, to clofazimine, and to highly bactericidal drugs like rifampicin. The use particularly of the more potent drugs in effective combinations and the development of standard multidrug therapy regimens have made a huge difference in the successful treatment of leprosy as well as in reducing tremendously the prevalence of leprosy globally. A major contributing factor to development of better drugs and drug combinations has been the introduction of the mouse footpad model to evaluate the in vivo activity of drugs against Mycobacterium leprae. The World Health Organization has recommended multidrug therapy, which has been used to treat more than 15 million patients in the last 30 years and has set an excellent record with regard to its very high rate of cure, very low occurrence of relapse, and very rare occurrence of drug resistance.

Case of tuberculosis acromioclavicular joint presenting as lytic lesion in lateral end clavicle: rare case report

Background: Rise in the incidence of tuberculosis (TB) seen in recent years. Skeletal TB accounts for less than 10% of all cases of TB. Most of these cases are in the spine and hip. The acromio-clavicular (AC) joint is a very uncommon site of skeletal TB. Case report: A 30 year old female developed pain in her right shoulder after sustaining trivial trauma. She was treated conservatively for six weeks, but patient complaints of increase in the intensity of pain with restricted movements. Radiographs repeated after six weeks showed a lytic lesion in the lateral end of clavicle with differential diagnosis of a solitary bone cyst or metastatic lesion. FNAC of the swelling done and MRI right shoulder advised. Histo-pathological report revealed evidence consistent with TB. The patient started on a multidrug anti-tubercular therapy (ATT) regimen with diagnosis of tuberculosis lateral end clavicle. MRI report after two weeks showed synovial hypertrophy and capsular distension with mild joint effusion in right AC joint. The diagnosis changed to tuberculosis of AC joint with continuation of the same treatment. Conclusion: The rarity of the occurrence of TB at unusual sites, and the ability of tuberculosis to mimic other diseases, combined with a lack of awareness by the treating orthopaedist often leads to diagnostic delays. A high index of suspicion should be maintained in cases of swellings around the shoulder, even if they lack systemic features of tuberculosis.rn

Induction of hypothyroidism in Hashimoto′s thyroiditis during leprosy treatment

We report a female case who developed hypothyroid in the course of multibacillary multidrug therapy regimen for leprosy. The evaluation was made to rule out the possible cause of rifampicin induced hypothyroidism in Hashimoto's thyroiditis.

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.